Investigating Coronary Artery Disease methylome through targeted bisulfite sequencing

Ghose, Subhoshree; Ghosh, Sourav; Tanwar, Vinay Singh; Tolani, Priya; Kutum, Rintu; Sharma, Anju; Bhardwaj, Nitin; Shamsudheen, K. V.; Verma, Ankit; Jayarajan, Rijith; Dash, Debasis; Sivasubbu, Sridhar; Scaria, Vinod; Seth, Sandeep; Sengupta, Shantanu

doi:10.1016/j.gene.2019.144107

Cited by 13 publications

(5 citation statements)

References 47 publications

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“…Of note, GALNT2 mRNA levels remain significantly associated with TG but no longer with HDL-C in conditional analyses including both lipid fractions, thus suggesting the association with HDL-C is mainly mediated by the very much expected strong and inverse correlation between HDL-C and TG levels [88]. Finally, the GALNT2 promoter is hyper-methylated, a proxy of gene down-regulation, in patients with CAD and low HDL-C levels [19,89].…”

Section: Galnt2 and Atherogenic Dyslipidemiamentioning

confidence: 97%

Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis

Antonucci

Marucci

Trischitta

et al. 2022

IJMS

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O-linked glycosylation, the greatest form of post-translational modifications, plays a key role in regulating the majority of physiological processes. It is, therefore, not surprising that abnormal O-linked glycosylation has been related to several human diseases. Recently, GALNT2, which encodes the GalNAc-transferase 2 involved in the first step of O-linked glycosylation, has attracted great attention as a possible player in many highly prevalent human metabolic diseases, including atherogenic dyslipidemia, type 2 diabetes and obesity, all clustered on the common ground of insulin resistance. Data available both in human and animal models point to GALNT2 as a molecule that shapes the risk of the aforementioned abnormalities affecting diverse protein functions, which eventually cause clinically distinct phenotypes (a typical example of pleiotropism). Pathways linking GALNT2 to dyslipidemia and insulin resistance have been partly identified, while those for type 2 diabetes and obesity are yet to be understood. Here, we will provide a brief overview on the present knowledge on GALNT2 function and dysfunction and propose novel insights on the complex pathogenesis of the aforementioned metabolic diseases, which all impose a heavy burden for patients, their families and the entire society.

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Section: Galnt2 and Atherogenic Dyslipidemiamentioning

confidence: 97%

Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis

Antonucci

Marucci

Trischitta

et al. 2022

IJMS

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“…Ghose, S. et al . reported that LDLR gene undergoes hypomethylation and induces an increased expression which subsequently decreases the LDL levels and reduces the risk of CAD 94 . In the present study, we have observed that 31% of CpG SNVs abolished the CGI existence and ~ 44% decreased the size of CGI.…”

Section: Discussionmentioning

confidence: 99%

In silico identification of single nucleotide variations at CpG sites regulating CpG island existence and size

Shyamala

Kongettira

Puranam

et al. 2022

Sci Rep

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Genetic and epigenetic modifications of genes involved in the key regulatory pathways play a significant role in the pathophysiology and progression of multifactorial diseases. The present study is an attempt to identify single nucleotide variations (SNVs) at CpG sites of promoters of ACAT1, APOB, APOE, CYBA, FAS, FLT1, KSR2, LDLR, MMP9, PCSK9, PHOX2A, REST, SH2B3, SORT1 and TIMP1 genes influencing CpG island (CGI) existence and size associated with the pathophysiology of Diabetes mellitus, Coronary artery disease and Cancers. Promoter sequences located between −2000 to + 2000 bp were retrieved from the EPDnew database and predicted the CpG island using MethPrimer. Further, SNVs at CpG sites were accessed from NCBI, Ensembl while transcription factor (TF) binding sites were accessed using AliBaba2.1. CGI existence and size were determined for each SNV at CpG site with respect to wild type and variant allele by MethPrimer. A total of 200 SNVs at CpG sites were analyzed from the promoters of ACAT1, APOB, APOE, CYBA, FAS, FLT1, KSR2, LDLR, MMP9, PCSK9, PHOX2A, REST, SH2B3, SORT1 and TIMP1 genes. Of these, only 17 (8.5%) SNVs were found to influence the loss of CGI while 70 (35%) SNVs were found to reduce the size of CGI. It has also been found that 59% (10) of CGI abolishing SNVs are showing differences in binding of TFs. The findings of the study suggest that the candidate SNVs at CpG sites regulating CGI existence and size might influence the DNA methylation status and expression of genes involved in molecular pathways associated with several diseases. The insights of the present study may pave the way for new experimental studies to undertake challenges in DNA methylation, gene expression and protein assays.

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“…[ 8 ] Finally, patients with coronary artery disease and low HDL‐C levels are characterized by GALNT2 promoter hyper‐methylation, a proxy of gene downregulation. [ 14 ] Taken altogether these data indicate that GALNT2 increases HDL‐C and decreases triglycerides serum levels and suggest that GALNT2 downregulation is a risk factor for atherogenic dyslipidemia.…”

Section: Introductionmentioning

confidence: 89%

Leveraging Genetics to Address the Role of GALNT2 on Atherogenic Dyslipidemia

et al. 2023

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Several studies have shown that downregulation of GALNT2 (Polypeptide N‐Acetylgalactosaminyltransferase 2), encoding polypeptide N‐acetylgalactosaminyltransferase 2, decreases high‐density lipoprotein cholesterol (HDL‐C) and increases triglycerides levels by glycosylating key enzymes of lipid metabolism, such as angiopoietin like 3, apolipoprotein C‐III, and phospholipid transfer protein. GALNT2 is also a positive modulator of insulin signaling and action, associated with in vivo insulin sensitivity and during adipogenesis strongly upregulates adiponectin. Thus, the hypothesis that GALNT2 affects HDL‐C and triglycerides levels also through insulin sensitivity and/or circulating adiponectin, is tested. In 881 normoglycemic individuals the G allele of rs4846914 SNP at the GALNT2 locus, known to associate with GALNT2 downregulation, is associated with low HDL‐C and high values of triglycerides, triglycerides/HDL‐C ratio, and theHomeostatic Model Assessment of insulin resistance HOMAIR (p‐values = 0.01, 0.027, 0.002, and 0.016, respectively). Conversely, no association is observed with serum adiponectin levels (p = 0.091). Importantly, HOMAIR significantly mediates a proportion of the genetic association with HDL‐C (21%, 95% CI: 7–35%, p = 0.004) and triglyceride levels (32%, 95% CI: 4–59%, p = 0.023). The results are compatible with the hypothesis that, besides the effect on key lipid metabolism enzymes, GALNT2 alters HDL‐C and triglyceride levels also indirectly through a positive effect on insulin sensitivity.

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Investigating Coronary Artery Disease methylome through targeted bisulfite sequencing

Cited by 13 publications

References 47 publications

Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis

Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis

In silico identification of single nucleotide variations at CpG sites regulating CpG island existence and size

Leveraging Genetics to Address the Role of GALNT2 on Atherogenic Dyslipidemia

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